It is important for active pharmaceutical ingredients (APIs) to be stable for prolonged periods of time. Generally, at least a two year shelf life is desirable as a raw bulk material or as a finished product or dosage form. Unfortunately, APIs often may not be stable alone or in combination with excipients that are used in dosage formulations such as tablets, capsules, films, etc.
Many API's may be unstable and degrade in the presence of oxygen. Oxygen sensitive API's may be stabilized by several different methods. For instance, the drug product and the API may be processed under inert atmospheres, e.g. under argon or nitrogen gas blankets, however, this requires special manufacturing conditions and adds to the cost of manufacturing a drug product. Antioxidants may be used to help stabilize oxygen sensitive API's. Useful antioxidants include bi-sulfites and ascorbic acid; however, there have been safety issues associated with the use of some antioxidants. In particular, sulfites have been determined to be harmful. Thus, the use of antioxidants is less desirable due to safety issues and it generally costs more than preparing a nasal spray solution under inert conditions.
Phenylephrine is an API used in pharmaceutical compositions as a decongestant. There has been increased use of phenylephrine in cold medications due to restrictions placed on the sale of compositions containing pseudoephedrine. However, phenylephrine is known to be unstable. This instability has been shown both in accelerated conditions of high humidity and temperature, but also in the presence of other incompatible inactive ingredients or active ingredients such as chlorpheniramine maleate. There are several nasal spray formulations for the treatment of nasal decongestion that contain phenylephrine. Marketed nasal sprays containing phenylephrine may be stabilized by manufacturing the spray under inert atmospheres, e.g. under argon or nitrogen gas blankets, which requires special manufacturing conditions and is costly.
US Published Patent Application 2006-0127473 discloses stabilized phenylephrine compositions comprising silicified microcrystalline cellulose.
Japanese Patent Application P2005-62094A discloses stabilized pharmaceutical compositions containing phenylephrine, carbinoxamine and citric acid.